DNA clamps could stop cancer in its tracks

A rendering of the nanometer-scale DNA clamp, that recognizes genetic mutations more strongly and specifically (Image: Marco Tripodi)

Scientists have developed a special DNA clamp to act as a diagnostic nano machine. It's capable of detecting genetic mutations responsible for causing cancers, hemophilia, sickle cell anemia and other diseases, more efficiently than existing techniques. Not only can the clamp be used to develop more advanced screening tests, but it could also help create more efficient DNA-based nano machines for targeted drug delivery.

To catch diseases at their earliest stages, researchers have begun looking into creating quick screening tests for specific genetic mutations that pose the greatest risk of developing into life-threatening illnesses. When the nucleotide sequence that makes up a DNA strand is altered, it is understood to be a mutation; specific types of cancers are understood to be caused by certain mutations. Even if one single nucelotide base has been inserted, deleted or changed, it can change the entire DNA sequence – scientists call this a single point mutation.

To detect this type of mutation and others, researchers typically use molecular beacons or probes, which are DNA sequences that become fluorescent on detecting mutations in DNA strands. The team of international researchers that developed the DNA clamp state that their diagnostic nano machine allows them to more accurately differentiate between mutant and non-mutant DNA.

"Our DNA clamp probes can perform very similar applications compared to molecular beacons, which are being used in many diagnostic clinics around the world since they enable the rapid, fluorescent detection of specific DNA sequences, or mutations," Alexis Vallée-Bélisle, a Chemistry Professor at the Université de Montréal, Canada tells Gizmag."However, since they bind DNA using a clamp mechanism, i.e. a single DNA sequence from a patient is recognized by two DNA sequences on our clamp, they are now able to detect single point mutations with much more efficiency than molecular beacons do."

According to the team, the DNA clamp is designed to recognize complementary DNA target sequences like a clamp-switch. As soon as it recognizes them, it binds with them to form a stable triple helix structure, while fluorescing at the same time. Being able to identify single point mutations more easily this way is expected to help doctors identify different types of cancer risks, with greater sensitivity, accuracy and precision, and to inform patients about the specific cancers they are likely to develop. Diagnosing cancer at a genetic level could potentially help arrest the disease, before it even develops properly.

"Cancer is a very complex disease that is caused by many factors," explains Vallée-Bélisle. "However, most of these factors are written in DNA. We only envisage identifying the cancers or potential of cancer. As our understanding of the effect of mutations in various cancer will progress, early diagnosis of many forms of cancer will become more and more possible."

Currently the team has only tested the probe on artificial DNA, and plans are in the works to undertake testing on human samples. The team believes that the DNA clamp will "provide a new weapon in the toolbox of nano engineers, to help them to design more efficient and versatile DNA nano machines." For instance, to deliver drugs to only the tumor cells, and not healthy cells, scientists can make use of DNA-based nano machines, that are created by assembling many different small DNA sequences together to create a 3D structure, kind of like a box. When it encounters a disease marker, the box opens up and delivers the drug, enabling smart drug delivery. The DNA clamps are expected to help this whole process function better.

"The clamp switches that we have designed and optimized can recognize a DNA sequence with high precision and high affinity," Professor Francesco Ricci, at the University of Rome,Tor Vergata, Italy, tells us."This means that our clamp switches can be used, for example, as super-glue to assemble these nano machines and create a better and more precise 3D structure that can, for example, open in the presence of a disease marker and release a drug."

The international research project was funded by the US National Institutes of Health, the Italian Ministry of Universities and Research (MIUR), the Natural Sciences and Engineering Research Council of Canada, the Bill & Melinda Gates Foundation Grand Challenges Explorations program and the European Commission Marie Curie Actions program. Their paper describing the development was recently published in the journal ACS Nano.